This proposal describes a 5 year training program for the development of an academic career in translational pain medicine research. The principal investigator has completed the MD/PhD program, residency in anesthesiology, and a pain medicine fellowship at the University of Texas Medical Branch (UTMB), and now will expand upon her scientific skills though an integration of interdepartmental resources. This program will promote the mastery of gene therapy as applied to neuropathic pain. Dr. Li- Yen Mae Huang will mentor the principal investigator's scientific development. She is a recognized leader in the field on pain research. Dr. Huang is a professor in the Department of Neurosciences and Cell Biology at UTMB and has trained numerous postdoctoral fellows and graduate students. This research will focus on strategies for treating chronic neuropathic pain conditions resulting from peripheral nerve injury. Previous laboratory studies using rat models have demonstrated an increase in the potency of morphine by inducing an over expression of opioid receptors. Numerous neuropathic pain models have been produced by peripheral nerve injury in rats. Yet, the lack of large animal models limits our ability to study the efficacy and safety of therapeutic alternatives prior to clinical trials. Therefore, the first step toward our overall goal is to develop a large animal neuropathic pain model in sheep. The second step is to induce gene expression in peripheral nerves as an approach to the treatment of chronic pain. This research postulates that the introduction of foreign genes into sensory neurons could serve as an endogenous source of therapeutic proteins, which could in turn increase the half-life of therapies and reduce systemic side effects. We will determine the safety and efficacy of such a gene therapeutic strategy in sheep. Since the same basic procedure to be used in humans will be used in sheep, the experiments will also allow us to test the procedure and feasibility prior to the development of a clinical trial. The combination of the Department of Anesthesiology and the Department of Neuroscience and Cell Biology at the University of Texas Medical Branch presents an ideal environment for training a physician-scientist by providing a multidisciplinary group of research investigators, extensive core facilities, and talented pain physicians. Such an environment also fosters the principal investigator's development of an independent research career. PUBLIC HEALTH RELEVANCE: The goal of the experiments is to find an effective strategy for treating chronic pain in patients with spinal cord or sciatic nerve injury. In this project, we will use a gene therapeutic strategy to deliver morphine receptors to the nerves in a large mammalian model. These experiments will allow us to test the procedure and assess the feasibility of the approach prior to a clinical trial.